Memory Loss: New Hope

Yale researchers have succeeded in restoring nerve networks in the brains of elderly animals to a more youthful state. Since these are networks known to be involved in memory storage and retrieval, this suggests that the loss of memory that accompanies aging can be reversed.

So far it works in animals. Tests in humans have just started.

By lowering the level of cyclic AMP or by blocking its effect, the researchers were able to get these nerve cells to fire faster in aged animals, much more like those of a young animal.

As people age, their memory and concentration begins to decline. This has been known for years, but the exact causes remain unknown. The Yale study suggest that one cause is a change in the chemical environment surrounding certain groups of brain cells and that changing that environment back helps restore some brain functions, including memory.

ADVERTISEMENT

Most nerve cells only fire in response to a cue or stimulus. Certain nerve cells in the brain's prefrontal cortex continually fire, even without a cue to stimulate them. They're thought to be responsible for working memory, the ability to keep information up to date even when it's constantly changing, like where you put your car keys or what mischief your two-year old toddler is up to. This firing affects more than memory; it's also needed for abstract thought, reasoning and other higher brain functions.

Working with animals, the researchers found that these constantly active nerve cells fired slower in older animals. They also found that in older animals, the nerve cells accumulated high levels of the cell-signaling molecule cyclic AMP. By lowering the level of cyclic AMP or by blocking its effect, the researchers were able to get these nerve cells to fire faster in aged animals, much more like those of a young animal.

Of course, animals don't carry car keys, so it's not known if this change helped the older animals keep track of them. That information will come from the human studies.

Cyclic AMP is a cytokine, a chemical messenger. It causes cells to change their behavior. In the prefrontal cortex, it causes nerve cells to open up ion channels, which weakens their firing and slows it down.

One of the compounds the researchers used that improved nerve firing is guanfasine. Guanfasine is a drug that has many different effects: it lowers blood pressure in adults and is sometimes used as a medication for hypertension. It's also used to treat attention deficit hyperactivity disorder (ADHD) in some children.

ADVERTISEMENT

Since guanfasine is already used as a drug, Yale was able to quickly start enrolling adults in a clinical trial that will test its ability to improve working memory and other higher brain functions in elderly adults. It may even help them find their car keys.

An article on the study was published online by Nature on July 27, 2011.